An Alternative Cell Therapy for Cancers: Induced Pluripotent Stem Cell (iPSC)-Derived Natural Killer Cells

Abstract

Cell therapy is usually defined as the treatment or prevention of human disease by supplementation with cells that have been selected, manipulated, and pharmacologically treated or altered outside the body (ex vivo). Induced pluripotent stem cells (iPSCs), with their unique characteristics of indefinite expansion in cultures and genetic modifications, represent an ideal cell source for differentiation into specialized cell types. Cell therapy has recently become one of the most promising therapeutic approaches for cancers, and different immune cell types are selected as therapeutic platforms. Natural killer (NK) cells are shown to be effective tumor cell killers and do not cause graft-vs-host disease (GVHD), making them excellent candidates for, and facilitating the development of, “off-the-shelf” cell therapies. In this review, we summarize the progress in the past decade in the advent of iPSC technology and review recent developments in gene-modified iPSC-NK cells as readily available “off-the-shelf” cellular therapies.

Advances in natural killer cell therapies for breast cancer

“…162 Fewer NK cells are generated from UCBs because of the UCB unit's modest volume. 157 UCB-derived NK cells had lower cytotoxicity against K562 cells than PB-derived NK cells because granzyme B in cord blood-NK cells is deficient. 163 According to published studies, UCB-derived NK cells express less CD16, DNAM-1, KIRs, IL-2R, NKG2C and granzyme B but more NKG2A, resulting in decreased effectiveness in killing target cells compared with PB-derived NK cells.…”

“…NK cells mature and enter the bloodstream from the bone marrow, lymph nodes, the spleen, tonsils and the thymus. 157 A clinically relevant number of functional NK cells capable of surviving in vivo is required for NK cell immunotherapy to be effective. Numerous attempts have been made to produce higher numbers of NK cells from various sources.…”

“…163 According to published studies, UCB-derived NK cells express less CD16, DNAM-1, KIRs, IL-2R, NKG2C and granzyme B but more NKG2A, resulting in decreased effectiveness in killing target cells compared with PB-derived NK cells. 157,163 However, when these cells were activated with cytokines, their cytotoxicity was comparable to that of PB-derived NK cells. 160,164 Peripheral blood-derived NK cells PB-NK cells are predominantly CD56 dim cells that are highly cytotoxic to target cells.…”

“…One study discovered that when UCB‐derived CD56 bright NK cells were treated with IL‐12 and IL‐18, they exhibited enhanced CD69 expression and produced significantly more IFNγ than PB‐NK cells 162 . Fewer NK cells are generated from UCBs because of the UCB unit's modest volume 157 . UCB‐derived NK cells had lower cytotoxicity against K562 cells than PB‐derived NK cells because granzyme B in cord blood‐NK cells is deficient 163 .…”

“…UCB‐derived NK cells had lower cytotoxicity against K562 cells than PB‐derived NK cells because granzyme B in cord blood‐NK cells is deficient 163 . According to published studies, UCB‐derived NK cells express less CD16, DNAM‐1, KIRs, IL‐2R, NKG2C and granzyme B but more NKG2A, resulting in decreased effectiveness in killing target cells compared with PB‐derived NK cells 157,163 . However, when these cells were activated with cytokines, their cytotoxicity was comparable to that of PB‐derived NK cells 160,164 …”